Receptor-mediated gonadotropic stimulation of adenylate cyclase and steroidogenic responses in the testis and ovary is followed by desensitization of the target-cell and turnover or processing of the hormone-receptor complex. These changes have been investigated in Leydig cells and ovarian granulosa cells to determine the effects of hormone-induced receptor regulation on gonadal responsiveness, and to analyze the mechanisms and consequences of target-cell stimulation and desensitization. In the rat ovary, the effects of FSH on granulosa-cell maturation have been shown to be mediated by cyclic AMP, and the inhibitory actions of GnRH agonists on this process are associated with decreased cAMP production. GnRH receptors in the granulosa cell were shown to mediate the prominent anti-gonadal actions of GnRH in the ovary, and GnRH agonists were found to inhibit FSH-stimulated adenylate cyclase activity both in vivo and in vitro. The inhibition of cAMP synthesis was largely due to a reduction in FSH receptor content. (In contrast, FSH was shown to up-regulate its homologous receptors, and those for GnRH). In addition to reducing cAMP synthesis, GnRH also increases cAMP catabolism, leading to reduced levels of the cyclic nucleotide and preventing cAMP-mediated cellular differentiation. The inhibitory effects of GnRH on LH-induced cAMP production were dependent on extracellular calcium, and were reproduced by the calcium ionophore A23187. Granulosa cell maturation and function were also influenced by other peptides including epidermal growth factor (EGF) and platelet derived growth factor (PDGF). Thus, EGF inhibited FSH-induced cAMP and progesterone production, and LH receptor formation, by inhibiting adenylate cyclase activity and stimulating a membrane phosphodiesterase. In contrast, PDGF enhanced FSH action by elevating cAMP accumulation, leading to elevated progesterone and LH receptor content. These findings indicate that the inhibitory effects of peptides such as GnRH and EGF in the granulosa cell are mediated by a calcium-dependent mechanism leading to impaired cAMP production and decreased expression of gonadotropin receptors.